By Rosemarie Tremblay-LeMay MD FRCPC
September 3, 2024
Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow. It specifically involves a type of white blood cell called a lymphocyte, which plays a crucial role in the immune system by helping the body fight infections. In this disease, the bone marrow produces too many abnormal lymphocytes and does not function properly. These abnormal lymphocytes build up over time, crowding out healthy blood cells and causing various health problems.
Chronic lymphocytic leukemia usually progresses slowly and may not cause symptoms for many years. It is the most common type of leukemia in adults, especially in older individuals. While some people with CLL may require treatment soon after diagnosis, others may not need treatment for many years and can be monitored with regular check-ups.
Common signs and symptoms of CLL include:
People with CLL may develop autoantibodies that cause the immune system to attack their own cells. This can lead to a type of anemia called hemolytic anemia, where red blood cells are destroyed. It can also lead to a disease called immune thrombocytopenia, which can result in bruising and bleeding. Many people can also have issues with their immune system that can make them vulnerable to infections.
The exact cause of CLL is not fully understood, but it involves a combination of genetic and environmental factors. Potential risk factors include:
It’s important to note that most people who develop CLL do not have any known risk factors, and it is not caused by lifestyle choices like diet or smoking. The disease is generally considered to arise from a complex interplay of genetic predisposition and environmental exposures.
When examined under the microscope, the tumour cells in CLL look the same as those found in another type of cancer called small lymphocytic lymphoma (SLL). The only real difference between CLL and SLL is where the tumour cells are found. When the tumour cells are found in the blood, the disease is called CLL. When the tumour cells are found in lymph nodes and other solid organs but not in the blood, the disease is called SLL. Because of these differences, SLL is classified as a type of lymphoma, while CLL is classified as a type of leukemia.
Patients with CLL can eventually develop SLL or vice versa, and they can present with both at the same time. For that reason, the disease is often described as CLL/SLL.
The diagnosis of CLL can be made after a blood test or after a small tissue sample is removed in a procedure called a biopsy. The tissue sample is often from the bone marrow or an enlarged lymph node. Your doctor may suspect that you have CLL if your blood test shows increased lymphocytes. Pathologists call this lymphocytosis. If lymphocytosis is found, another test called flow cytometry may be performed on your blood sample. This test allows your pathologist to determine if the lymphocytes are abnormal. See the Flow cytometry section below for more information.
When examined under the microscope, the cancer cells in the blood are small and have little substance in a part of their cell body called the cytoplasm. The cells are fragile and tend to break when the blood is spread on a glass slide. Pathologists call these broken cells smudge cells. Instead of being evenly spread out, the genetic material or chromatin in the nucleus of the cell will also appear as small dots. Pathologists describe this look as clumpy and may say that the chromatin resembles a soccer ball (dark dots on a pale background).
Your pathologist will perform a test called immunohistochemistry to learn more about the tumour and exclude other diseases that can look similar to CLL under the microscope. Immunohistochemistry allows pathologists to see the different types of proteins produced by cells in a tissue sample. Pathologists describe the result as positive or reactive when the cells produce a protein. When the cells do not make the protein, the result is described as negative or non-reactive.
Because the cancer cells in CLL come from specialized immune cells called B cells, they produce proteins normally made by this type of cell. These proteins include CD20, CD19, PAX5, and CD79a. The expression of CD20 is usually weaker than normal, healthy B cells. The cancer cells also usually produce CD5, CD23, CD43, and LEF1. CD10 and CyclinD1 are found in other types of B-cell lymphomas and are not produced by the cancer cells in CLL.
Flow cytometry is a special test used to examine immune cells in blood, bone marrow, or tissue samples. Another name for this test is flow immunophenotyping. Unlike other laboratory tests, flow cytometry can quickly examine millions of individual cells and collect information about each cell. The information collected includes the cell size and shape and the types of proteins each cell makes.
When examined by flow cytometry, the tumour cells in CLL will have strong expression of the protein CD200. Expression of the protein CD38 in more than 30% of the tumour cells can be associated with more aggressive disease.
Each cell in your body contains a set of instructions that tell it how to behave. These instructions are written in a language called DNA and stored on 46 chromosomes in each cell. Because the instructions are very long, they are broken up into sections called genes, and each gene tells the cell how to produce a piece of the machine called a protein.
Pathologists test for changes involving chromosomes by performing fluorescence in situ hybridization (FISH). When FISH is performed on CLL, an abnormal number of chromosomes may be found. The test may also show that a piece of a chromosome has been lost.
The most common changes seen in CLL are:
Tumours that have lost part of chromosome 11 or chromosome 17, and those that show complex changes (multiple gains or losses), can behave more aggressively than tumours without these changes.
Some tumours will show a change (a mutation) in a gene called immunoglobulin heavy chain. This gene produces a protein that helps B cells recognize foreign proteins in the body (such as those on viruses). Tumours with this mutation are less aggressive and may have a more favorable prognosis compared to tumours without the mutation.
A small number of larger lymphocytes called prolymphocytes are also usually seen. These cells typically make up less than 15% of the cancer cells seen in the sample. If the number of prolymphocytes is greater than 15% but is still less than 55%, your pathologist will describe the changes as atypical CLL.
Atypical CLL cells are more likely to have an extra copy of chromosome 12 (trisomy 12) and may produce proteins that are not typically produced by CLL cells. If more than 55% of the cancer cells in the sample are prolymphocytes, the diagnosis changes to B-cell prolymphocytic leukemia, a different, more aggressive type of cancer.
Cancer cells seen in a tissue sample, such as a lymph node, are very similar to those seen in the blood. They are mostly small, except for groups of larger cells called proliferation centers.
Over time, CLL can change into a more aggressive type of lymphoma. Pathologists call this a transformation. Your pathologist will carefully examine the sample for evidence of transformation.
CLL can transform in one of three ways:
Because these conditions are more aggressive, they require different treatment than CLL without transformation.
Doctors wrote this article to help you read and understand your pathology report. Contact us with any questions about this article or your pathology report. Read this article for a more general introduction to the parts of a typical pathology report.